Triple-therapy regimen bested standard regimen in lowering HIV transmission when nursing

Farley T. The Lancet.2011.doi:10.1016/S1473-3099(10)70288-7.

Issue: February 2011

WHO researchers recommend triple-antiretroviral prophylaxis — as opposed to the standard regimen — after finding that it reduced the risk for HIV-1 transmission from mother-to-child during nursing by as much as 53%.

“Infants born to HIV-positive mothers can now benefit from all advantages of breast milk,” Timothy Farley, PhD,of the department of reproductive health and research at the WHO, told Infectious Disease News. “Early referral in pregnancy for HIV testing and CD4 count, or even HIV diagnosis and CD4 count before pregnancy for optimal maternal health and a safe and successful pregnancy [is recommended].”

Researchers for the Kesho Bora Study examined whether a combination of three antiretroviral drugs assigned during pregnancy, delivery and nursing were more effective at preventing mother-to-child HIV transmission when compared with a standard therapy regimen. The cohort included 824 HIV-positive pregnant women from five study sites in Kenya and South Africa with CD4 cell counts between 200 and 500 cells per mcL.

Women were randomly assigned to either a combination of 300 mg zidovudine plus 150 mg lamivudine and 400 mg lopinavir, boosted with 100 mg ritonavir twice-daily, or to a standard therapy regimen of 300 mg zidovudine twice-daily until delivery plus single-dose 200 mg nevirapine during labor. The three-drug regimen was initiated during 28 and 34 weeks of pregnancy until cessation of nursing or 6.5 months post-partum. Infants were given 0.6 mL nevirapine at birth and 4 mg zidovudine for one week after birth.

At 6 weeks, the cumulative rate for HIV-transmission in the triple-therapy regimen group was 3.3% (95% CI; 1.9-5.6) compared with 5% (95% CI, 3.3-7.7) in the standard therapy group. The risk for transmission during nursing at 6 weeks was 53% lower in the triple-therapy regimen group (2.2% vs. 4.7%; P=.049).

At 1 year, HIV transmission was 5.4% in the triple-drug regimen group vs. 9.5% in the standard regimen (P=.029) — a 43% lower rate for HIV transmission in those assigned the triple-therapy regimen.

Both therapy regimens were safe, with no differences in serious adverse events, according to the researchers.

This study addresses a really challenging problem having much to do with resources as much as science. It should be no surprise that a multi-drug combination therapy when used in women that are pregnant or breast feeding is Iess effective at stopping transmission of HIV. We've known this for a long time. There is a lot of data accumulated over the years that lesser potent approaches can be partially effective, such as single agent verapine, or as studied initially in this country, AZT at the time of delivery, can decrease transmission. But, all of our data on treatment-infected adults and children suggests that the patient will do better with combination therapy and this study shows that this is true for women who are nursing. Again, not surprising, but it's important because policy makers need this type of data to help make those decisions. Three-drug therapy is more expensive, but it works better and this is the bottom line.

–Paul Volberding, MD

Infectious Disease News Editorial Board member

Disclosures: Dr. Farley has no direct financial interest in any of the products mentioned in this article nor is he a paid consultant for any companies mentioned.

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